The Washington University DNA Sequencing Center has three projects with the following goals: 1) Complete half the sequence of the l00 Mb Caenorhabditis elegans genome, which, when combined with the results from a collaborative effort by John Sulston and his colleagues at the Sanger Centre of Cambridge, England, will complete the genomic sequence for this important experimental animal. 2) Aid in the completion of the yeast S. cerevesiae genomic sequence through the contribution of 3 Mb of sequence in the first two years of the project. The interpretation of the sequence will be improved by a small project to systematically alter expression of the genes in the sequenced regions. 3) Initiate a three-year pilot project to sequence human DNA. In the first year, effort will focus on the region of chromosome 16p which harbors the gene for autosomal dominant polycystic kidney disease. In years two and three, attention will shift to gene-rich regions of chromosome 7 that are medically important. The activities of the Center are supported by four Cores, including a Development Core devoted to the implementation of robotics and technological improvements that are devised either here (in collaboration with our Cambridge colleagues) or by other laboratories. The Center represents a highly ambitious undertaking that will both produce DNA sequence of great value to the biological and medical communities and serve as a major focus for the sequencing component of the Human Genome Project.